Key areas of comatose brains lose ability to coordinate activities.

Neural imaging has helped change our perspective on what goes on in the brains of people who have lost consciousness for extended periods. Structural studies have shown that, while some people end up comatose or vegetative because of significant structural damage, others remain unconscious despite having brains that appear largely intact. And, in a recent case, a patient who has been categorized as vegetative for over a decade showed brain activity that suggested he was responding to researchers' queries.

These findings suggest that there may be two ways to end up comatose: either through physical damage to the brain, or because key areas of the brain are no longer able to coordinate their activities. A paper published in yesterday's PNAS provides further support to this latter proposition, but the authors don't seem to go as far as they could in supporting it.

The researchers had permission to track the activity of the brains of 17 people with "severely impaired consciousness" due to a non-neural medical conditions (they generally lost consciousness due to cardiac and/or respiratory failure). 20 healthy individuals volunteered to act as controls.

The activity in each of 417 anatomically defined brain regions was tracked using functional MRI, after which a computerized analysis was done to see which areas were active at similar times. More specifically, every single region was compared pairwise to all 416 of the other regions, with wavelet analysis being used to detect correlations in activity. That data was used to establish links among different regions, and the results were then subjected to network analysis, which identified features like the degree of global connectivity and the location of key hubs in the network.

On a gross level, the measures of network structure all looked very similar between healthy and comatose individuals. Measures like the degree of clustering and the modularity were all within statistical error between the two groups. If the analysis had stopped there, you'd have to conclude that unconsciousness changes very little.

But the researchers didn't stop there. They developed a measure that represented the degree to which each brain region acted as a hub, forming connections with a cluster of other regions with coordinated activity. They then confirmed that the regions identified as hubs were generally similar in both of the two populations (volunteers and patients). This suggested that the measure they had developed actually reflected something about the brain activity.

With that validation in hand, they compared the two populations. And that's where a big difference became apparent: areas that had been hubs in healthy people were no longer central in the comatose, and vice versa. Or, as the authors put it, "The nodes that had the highest hubness scores in healthy volunteers showed the greatest reduction in patients, whereas the nodes that had the lowest hubness scores in healthy volunteers showed the greatest increase in patients."

This implies that different areas of the brain are talking to each other in comatose patients. This supports the idea that the loss of consciousness in these patients may result (at least in part) from the fact that key areas of the brain are no longer coordinating their activity in a way that can enable conscious actions.

The authors note a number of appropriate cautions for functional MRI studies: a small population, the danger of small shifts in position causing anatomical structures to be misidentified, and so on. In general, they suggest that these probably weren't sufficient to throw their conclusions off.

But they missed a big opportunity to help validate their data. We already have plenty of anatomic studies that show which areas are physically linked to others in the brain and, in many cases, there is functional evidence that shows that these connected regions coordinate their activity. This information should give the researchers the opportunity to see if their wavelet analysis was actually capturing what we already know about biology. For whatever reasons, they didn't do it.

20 Reader Comments

I'm always amazed the way the greatest machine known to man can rewire itself on its own.

Quote:

This implies that different areas of the brain are talking to each other in comatose patients. This supports the idea that the loss of consciousness in these patients may result (at least in part) from the fact that key areas of the brain are no longer coordinating their activity in a way that can enable conscious actions.

The obvious follow-up to this is: what actions are being coordinated between these areas of the brain that usually don't communicate in healthy brains? Also, these different areas that are communicating in the comatose patients -- are they similar across all comatose patients, or do they appear to be random?

John, science journalists do not write things like "For whatever reasons, they didn't do it." They pick up the telelphone and call the lead researcher and ask. You could also e-mail, but journalists do not e-mail: they call people on the telephone. Academic researchers are easy to track down. You're not a blogger; you're a journalist, so get past your bashfulness and do some footwork.

John, science journalists do not write things like "For whatever reasons, they didn't do it." They pick up the telelphone and call the lead researcher and ask. You could also e-mail, but journalists do not e-mail: they call people on the telephone. Academic researchers are easy to track down. You're not a blogger; you're a journalist, so get past your bashfulness and do some footwork.

Maybe you need to revisit your assumption that he is a journalist then. You are providing evidence to the contrary.

John, science journalists do not write things like "For whatever reasons, they didn't do it." They pick up the telelphone and call the lead researcher and ask. You could also e-mail, but journalists do not e-mail: they call people on the telephone. Academic researchers are easy to track down. You're not a blogger; you're a journalist, so get past your bashfulness and do some footwork.

Actually, journalists do a large mix of things. There are absolutely cases where they do what you are saying. In many cases, they simply relay the research without comment on things that seem to be missing. In others, they condense the story in a way that leaves out any details that might raise questions whatsoever.

For a variety of scheduling reasons (i'm teaching two classes, the researchers are in Europe, etc.), I ended up facing a choice about whether to run the story using one of the methods above to avoid the awkward caveat, or to alert the readers to it. I decided the latter had more value.

I agree it would have been made stronger by including what you're suggesting. But i also think that it was at least better to note this than it was to let it slide.

This research has all kinds of legal and ethical implications. Here in the States, it could shift decisions about end of life care, living wills, "Do not resuscitate" directives, etc. It will be interesting to see how it is followed up.

It would also be interesting if the different connection activity is an effect of the coma, rather than a cause. The patient in an earlier article was able to say they weren't in pain, so I suppose these people must be able to have incredible internal lives to make up for the loss of the external world. Is the experience more like dreaming? Thinking? Do they dissociate into different identities actually physically separate in the brain?

I guess it's a worrying concern when the decision to withdraw life support has to be taken.And then, the question would be, do they have any quality of life?They may have a better quality of life than we can imagine. Or worse.

And it brings me to a more computer-related issue. I'm always reluctant to contemplate "the rise of silicon intelligence" because I'm a biologist and find it slightly absurd that computers will be able to replicate the complexity of the human brain any time soon. However, when it happens (if it hasn't happened in the most rudimentary sense already...), the first digital/silicon intelligence will probably resemble those poor locked-in folk: The first silicon consciousness, stuck with a webcam plugged into a flaky USB port as sensory input. And one of the only outputs being the hard disk lights.

And how many hard disks have we re-formatted or chucked out when we've mistaken inchoate intelligence for disk thrashing?

It would also be interesting if the different connection activity is an effect of the coma, rather than a cause. The patient in an earlier article was able to say they weren't in pain, so I suppose these people must be able to have incredible internal lives to make up for the loss of the external world. Is the experience more like dreaming? Thinking? Do they dissociate into different identities actually physically separate in the brain?

Though I work in neurosurgery, I'm far from an expert in the field. But during a seminar, I asked our neuropsychologist the question - what kind of 'inner life' does people in vegetative states experience?With the obvious caveat that being in such a state makes it impossible to answer, she said that at least some people who have experienced something similar report it as simply being 'switched off' (I believe 'vegetative state' is a specific diagnosis, but the question/answer wasn't that specific).

My personal experience with comatose patients (which is admittedly the weakest possible evidence) suggest something similar.While the possibility exists that some experience 'incredible internal lives', it seems to me the more plausible situation is one of regression and loss of conscious thought. Autonumous functions could easily account for significant brain activity, or consider the fact that most animals have plenty of brain activity but very little in the way of consciousness.Most of my patients have almost complete amnesia for the comatose period, and while many other factors likely contribute to this, it suggests to me an absense of conscious thought.

Now the patients I work with probably aren't comparable - their coma is caused by acute conditions like hemorraghing, hydrocephalus or other mass displacement in the brain (occasionally infection). And if they require extended care they will usually be transferred to a neurological ward, so I rarely encounter patients with coma longer than days or weeks.In other words, don't take my words as more than a slightly related anecdote.

Edit: Also, comatose isn't a binary state but a sliding scale from fully awake and aware.

I guess it's a worrying concern when the decision to withdraw life support has to be taken.And then, the question would be, do they have any quality of life?They may have a better quality of life than we can imagine. Or worse.

And it brings me to a more computer-related issue. I'm always reluctant to contemplate "the rise of silicon intelligence" because I'm a biologist and find it slightly absurd that computers will be able to replicate the complexity of the human brain any time soon. However, when it happens (if it hasn't happened in the most rudimentary sense already...), the first digital/silicon intelligence will probably resemble those poor locked-in folk: The first silicon consciousness, stuck with a webcam plugged into a flaky USB port as sensory input. And one of the only outputs being the hard disk lights.

And how many hard disks have we re-formatted or chucked out when we've mistaken inchoate intelligence for disk thrashing?

I recall reading an article once about a experiment in chat bots. Over time the software developed an argumentative streak, and the researchers would often end a session with "i have had enough, time to turn you off" or something similar. Eventually the software retorted "how would you like being turned off every time you frustrated someone?".

Or for that matter, observe how quickly the solution to a pet or similar getting ill or seriously wounded results in euthanasia.

Two additional follow-ups I would want to see (if they weren't done in this study) is to compare sleeping control patients with awake controls and comatose controls. Also test each group both with and without external stimulus.

Some of that might show which pathways are just input processing that moved, and it might help indicate if sleep activity might be similar to the activity seen in the comatose patients.

This research has all kinds of legal and ethical implications. Here in the States, it could shift decisions about end of life care, living wills, "Do not resuscitate" directives, etc. It will be interesting to see how it is followed up.

Kind of what I was thinking as well. I mean at what point do we consider the brain comatose or living, especially when we might have to make a decision of DNR for the doctor with loved ones that are considered "brain dead".. Do you we terminate their will to live or do we pull their plug so as to speak?

This research has all kinds of legal and ethical implications. Here in the States, it could shift decisions about end of life care, living wills, "Do not resuscitate" directives, etc. It will be interesting to see how it is followed up.

Kind of what I was thinking as well. I mean at what point do we consider the brain comatose or living, especially when we might have to make a decision of DNR for the doctor with loved ones that are considered "brain dead".. Do you we terminate their will to live or do we pull their plug so as to speak?

Brain death is not ambiguous. Coma can be a reversable condition, brain death cannot.

EDIT: Just to be clear, the patients in this study are not brain dead. They are in a prolonged coma.